Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Virginie J.M. Verhoeven; Pirro G. Hysi; Robert Wojciechowski; Qiao Fan; Jeremy A. Guggenheim; René Höhn; Stuart Macgregor; Alex W. Hewitt; Abhishek Nag; Ching Yu Cheng; Ekaterina Yonova-Doing; Xin Zhou; M. Kamran Ikram; Gabriëlle H.S. Buitendijk; George Mcmahon; John P. Kemp; Beate St Pourcain; Claire L. Simpson; Kari Matti Mäkelä; Terho Lehtimäki; Mika Kähönen; Andrew D. Paterson; S. Mohsen Hosseini; Hoi Suen Wong; Liang Xu; Jost B. Jonas; Olavi Pärssinen; Juho Wedenoja; Shea Ping Yip; Daniel W.H. Ho; Chi Pui Pang; Li Jia Chen; Kathryn P. Burdon; Jamie E. Craig; Barbara E.K. Klein; Ronald Klein; Toomas Haller; Andres Metspalu; Chiea Chuen Khor; E. Shyong Tai; Tin Aung; Eranga Vithana; Wan Ting Tay; Veluchamy A. Barathi; Peng Chen; Ruoying Li; Jiemin Liao; Yingfeng Zheng; Rick T. Ong; Angela Döring; David M. Evans; Nicholas J. Timpson; Annemieke J.M.H. Verkerk; Thomas Meitinger; Olli Raitakari; Felicia Hawthorne; Tim D. Spector; Lennart C. Karssen; Mario Pirastu; Federico Murgia; Wei Ang; Aniket Mishra; Grant W. Montgomery; Craig E. Pennell; Phillippa M. Cumberland; Ioana Cotlarciuc; Paul Mitchell; Jie Jin Wang; Maria Schache; Sarayut Janmahasathian; Robert P. Igo; Jonathan H. Lass; Emily Chew; Sudha K. Iyengar

doi:10.1038/ng.2554

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Virginie J.M. Verhoeven, Pirro G. Hysi, Robert Wojciechowski, Qiao Fan, Jeremy A. Guggenheim, René Höhn, Stuart Macgregor, Alex W. Hewitt, Abhishek Nag, Ching Yu Cheng, Ekaterina Yonova-Doing, Xin Zhou, M. Kamran Ikram, Gabriëlle H.S. Buitendijk, George Mcmahon, John P. Kemp, Beate St Pourcain, Claire L. Simpson, Kari Matti Mäkelä, Terho LehtimäkiMika Kähönen, Andrew D. Paterson, S. Mohsen Hosseini, Hoi Suen Wong, Liang Xu, Jost B. Jonas, Olavi Pärssinen, Juho Wedenoja, Shea Ping Yip, Daniel W.H. Ho, Chi Pui Pang, Li Jia Chen, Kathryn P. Burdon, Jamie E. Craig, Barbara E.K. Klein, Ronald Klein, Toomas Haller, Andres Metspalu, Chiea Chuen Khor, E. Shyong Tai, Tin Aung, Eranga Vithana, Wan Ting Tay, Veluchamy A. Barathi, Peng Chen, Ruoying Li, Jiemin Liao, Yingfeng Zheng, Rick T. Ong, Angela Döring, David M. Evans, Nicholas J. Timpson, Annemieke J.M.H. Verkerk, Thomas Meitinger, Olli Raitakari, Felicia Hawthorne, Tim D. Spector, Lennart C. Karssen, Mario Pirastu, Federico Murgia, Wei Ang, Aniket Mishra, Grant W. Montgomery, Craig E. Pennell, Phillippa M. Cumberland, Ioana Cotlarciuc, Paul Mitchell, Jie Jin Wang, Maria Schache, Sarayut Janmahasathian, Robert P. Igo, Jonathan H. Lass, Emily Chew, Sudha K. Iyengar

Research output: Journal article publication › Journal article › Academic research › peer-review

354 Citations (Scopus)

Abstract

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

Original language	English
Pages (from-to)	314-318
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	3
DOIs	https://doi.org/10.1038/ng.2554
Publication status	Published - 1 Mar 2013

ASJC Scopus subject areas

Genetics

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10.1038/ng.2554

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Verhoeven, V. J. M., Hysi, P. G., Wojciechowski, R., Fan, Q., Guggenheim, J. A., Höhn, R., Macgregor, S., Hewitt, A. W., Nag, A., Cheng, C. Y., Yonova-Doing, E., Zhou, X., Ikram, M. K., Buitendijk, G. H. S., Mcmahon, G., Kemp, J. P., Pourcain, B. S., Simpson, C. L., Mäkelä, K. M., ... Iyengar, S. K. (2013). Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nature Genetics, 45(3), 314-318. https://doi.org/10.1038/ng.2554

@article{4d1a011588e54c7d8a7f00b0c8e20a37,

title = "Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia",

abstract = "Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.",

author = "Verhoeven, {Virginie J.M.} and Hysi, {Pirro G.} and Robert Wojciechowski and Qiao Fan and Guggenheim, {Jeremy A.} and Ren{\'e} H{\"o}hn and Stuart Macgregor and Hewitt, {Alex W.} and Abhishek Nag and Cheng, {Ching Yu} and Ekaterina Yonova-Doing and Xin Zhou and Ikram, {M. Kamran} and Buitendijk, {Gabri{\"e}lle H.S.} and George Mcmahon and Kemp, {John P.} and Pourcain, {Beate St} and Simpson, {Claire L.} and M{\"a}kel{\"a}, {Kari Matti} and Terho Lehtim{\"a}ki and Mika K{\"a}h{\"o}nen and Paterson, {Andrew D.} and Hosseini, {S. Mohsen} and Wong, {Hoi Suen} and Liang Xu and Jonas, {Jost B.} and Olavi P{\"a}rssinen and Juho Wedenoja and Yip, {Shea Ping} and Ho, {Daniel W.H.} and Pang, {Chi Pui} and Chen, {Li Jia} and Burdon, {Kathryn P.} and Craig, {Jamie E.} and Klein, {Barbara E.K.} and Ronald Klein and Toomas Haller and Andres Metspalu and Khor, {Chiea Chuen} and Tai, {E. Shyong} and Tin Aung and Eranga Vithana and Tay, {Wan Ting} and Barathi, {Veluchamy A.} and Peng Chen and Ruoying Li and Jiemin Liao and Yingfeng Zheng and Ong, {Rick T.} and Angela D{\"o}ring and Evans, {David M.} and Timpson, {Nicholas J.} and Verkerk, {Annemieke J.M.H.} and Thomas Meitinger and Olli Raitakari and Felicia Hawthorne and Spector, {Tim D.} and Karssen, {Lennart C.} and Mario Pirastu and Federico Murgia and Wei Ang and Aniket Mishra and Montgomery, {Grant W.} and Pennell, {Craig E.} and Cumberland, {Phillippa M.} and Ioana Cotlarciuc and Paul Mitchell and Wang, {Jie Jin} and Maria Schache and Sarayut Janmahasathian and Igo, {Robert P.} and Lass, {Jonathan H.} and Emily Chew and Iyengar, {Sudha K.}",

year = "2013",

month = mar,

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doi = "10.1038/ng.2554",

language = "English",

volume = "45",

pages = "314--318",

journal = "Nature Genetics",

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Verhoeven, VJM, Hysi, PG, Wojciechowski, R, Fan, Q, Guggenheim, JA, Höhn, R, Macgregor, S, Hewitt, AW, Nag, A, Cheng, CY, Yonova-Doing, E, Zhou, X, Ikram, MK, Buitendijk, GHS, Mcmahon, G, Kemp, JP, Pourcain, BS, Simpson, CL, Mäkelä, KM, Lehtimäki, T, Kähönen, M, Paterson, AD, Hosseini, SM, Wong, HS, Xu, L, Jonas, JB, Pärssinen, O, Wedenoja, J, Yip, SP, Ho, DWH, Pang, CP, Chen, LJ, Burdon, KP, Craig, JE, Klein, BEK, Klein, R, Haller, T, Metspalu, A, Khor, CC, Tai, ES, Aung, T, Vithana, E, Tay, WT, Barathi, VA, Chen, P, Li, R, Liao, J, Zheng, Y, Ong, RT, Döring, A, Evans, DM, Timpson, NJ, Verkerk, AJMH, Meitinger, T, Raitakari, O, Hawthorne, F, Spector, TD, Karssen, LC, Pirastu, M, Murgia, F, Ang, W, Mishra, A, Montgomery, GW, Pennell, CE, Cumberland, PM, Cotlarciuc, I, Mitchell, P, Wang, JJ, Schache, M, Janmahasathian, S, Igo, RP, Lass, JH, Chew, E & Iyengar, SK 2013, 'Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia', Nature Genetics, vol. 45, no. 3, pp. 314-318. https://doi.org/10.1038/ng.2554

TY - JOUR

T1 - Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

AU - Verhoeven, Virginie J.M.

AU - Hysi, Pirro G.

AU - Wojciechowski, Robert

AU - Fan, Qiao

AU - Guggenheim, Jeremy A.

AU - Höhn, René

AU - Macgregor, Stuart

AU - Hewitt, Alex W.

AU - Nag, Abhishek

AU - Cheng, Ching Yu

AU - Yonova-Doing, Ekaterina

AU - Zhou, Xin

AU - Ikram, M. Kamran

AU - Buitendijk, Gabriëlle H.S.

AU - Mcmahon, George

AU - Kemp, John P.

AU - Pourcain, Beate St

AU - Simpson, Claire L.

AU - Mäkelä, Kari Matti

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Paterson, Andrew D.

AU - Hosseini, S. Mohsen

AU - Wong, Hoi Suen

AU - Xu, Liang

AU - Jonas, Jost B.

AU - Pärssinen, Olavi

AU - Wedenoja, Juho

AU - Yip, Shea Ping

AU - Ho, Daniel W.H.

AU - Pang, Chi Pui

AU - Chen, Li Jia

AU - Burdon, Kathryn P.

AU - Craig, Jamie E.

AU - Klein, Barbara E.K.

AU - Klein, Ronald

AU - Haller, Toomas

AU - Metspalu, Andres

AU - Khor, Chiea Chuen

AU - Tai, E. Shyong

AU - Aung, Tin

AU - Vithana, Eranga

AU - Tay, Wan Ting

AU - Barathi, Veluchamy A.

AU - Chen, Peng

AU - Li, Ruoying

AU - Liao, Jiemin

AU - Zheng, Yingfeng

AU - Ong, Rick T.

AU - Döring, Angela

AU - Evans, David M.

AU - Timpson, Nicholas J.

AU - Verkerk, Annemieke J.M.H.

AU - Meitinger, Thomas

AU - Raitakari, Olli

AU - Hawthorne, Felicia

AU - Spector, Tim D.

AU - Karssen, Lennart C.

AU - Pirastu, Mario

AU - Murgia, Federico

AU - Ang, Wei

AU - Mishra, Aniket

AU - Montgomery, Grant W.

AU - Pennell, Craig E.

AU - Cumberland, Phillippa M.

AU - Cotlarciuc, Ioana

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Schache, Maria

AU - Janmahasathian, Sarayut

AU - Igo, Robert P.

AU - Lass, Jonathan H.

AU - Chew, Emily

AU - Iyengar, Sudha K.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

AB - Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

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U2 - 10.1038/ng.2554

DO - 10.1038/ng.2554

M3 - Journal article

C2 - 23396134

SN - 1061-4036

VL - 45

SP - 314

EP - 318

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

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